The goal of these studies is to understand the relationships of streptococcal bacteriophages, bacteriocins and genetic changes to the epidemiology of group A streptococcal infections and to the pathogenesis of their nonsuppurative sequelae (glomerulonephritis, rheumatic fever and rheumatic heart disease). Phage subtyping systems will be developed and applied to strains from patients (and from epidemics) with and without renal and cardiac complications. Temperate phages from these strains, well-documented as to their clinical and epidemiological source, will be compared with respect to their host range, immunologic specificity and DNA sequence (by restriction endonuclease analysis). Determinants of the immunologic specificity of phages from large numbers of strains will be facilitated by the development of an enzyme-linked immunoabsorbant assay (ELISA) for phage-associated hyaluronidases, which appear to be remarkably diverse and to parallel the M protein of their host strain in their immunological specificity. An ELISA for phage hyaluronidases will also provide a sensitive method for screening human sera for antibody to specific phages from strains associated (and not associated) with non-suppurative complications. The presence or absence of well characterized specific phages in induced lysates will be related to the production by their host strains of specific bacteriocin(s) and of a unique nephritis-strain associated protein (NSAP), the detection and quantitation of which will be facilitated by the development of specific ELISA's for these products, using monoclonal antibodies. Genetic changes in streptococci (by transduction, lysogenic conversion or conjugation) that may modify their pathogenic properties, such as production of bacteriocins and NSAP, will also be studied.